There are ~430,000 patients with End Stage Renal Disease (ESRD) in the US on hemodialysis (HD) accounting for > 6% of all Medicare spending ($34B). Home hemodialysis (HHD) is both less expensive than in-center dialysis (ICHD) and beneficial to patients because it enables more frequent dialysis. Despite these benefits HHD adoption is low (1.5%) in part because of the complexity and safety concerns associated with patient managed dialysis. This proposal will test the hypothesis that a novel, highly permeable dialysis membrane technology (silicon nanomembranes) can reduce the amount of membrane area required for hemodialysis 100 fold. Such a breakthrough can help drive the adoption of HHD by dramatically changing the format for dialysis by enabling smaller and wearable devices, shorter and more effective dialysis times, and simpler systems. Aim 1 will use bench top studies to establish a preliminary optimum operational conditions (flow rates, membrane properties) that maximize urea clearance while achieving ideal ultrafiltration rates. Aim 2 will use the bench top optimization from Aim 1 as a baseline condition for small animal studies (rats). Rats will be made uremic through diet and hemodialysis experiments with nanomembranes will again identify an optimum condition for urea clearance. Studies will also measure middle weight protein clearance, albumin retention, ultrafiltration and cellular and protein activation. All resuts will be compared directly to results with conventional HD membranes. Our hypothesis will be supported if the membrane surface area required for a therapeutic reduction of urea (KT/V = 1.2) is 100x less for silicon nano membranes than for conventional membranes. The studies are motivated by promising preliminary findings in a small animal model performed under non-optimized conditions.